Choroidal NeoVascularization (CNV) occurring in wet age-related macular degeneration (AMD) and diabetic proliferative retinopathy (DPR) is a chronic process leading to severe visual loss and blindness. CNV is characterized by growth of abnormal, new blood vessels from the choriocapillaris through defects in the Bruch's membrane into the sub-retinal space. The products currently in development are significantly compromised by the requirement for repeated and inconvenient intraocular injection. Thus, a better delivery system is needed. The strategy of treating CNV with anti-angiogenic factors is very promising. CytoPro aims the strategy that a single intra-ocular administration of a gene transfer vector will provide sustained delivery of a therapeutic, antiangiogenic protein selectively to the retina. CytoPro is now developing an advanced gene transfer system for potent anti-angiogenic transgenes to rapidly develop a superior product and to market it for CNV treatments. The goal of Phase I study of this SBIR project in the next few months is to develop a Cyto-PO promoter derived from human Pax6 PO promoter for gene delivery and expression using a lentiviral transfer system. In phase I of the project, we plan to: 1) optimize the efficiency and retina-specificity of the Cyto-PO promoter; 2) replace the viral origin CMV promoter in the lentiviral transfer vector; and 3) evaluate the specificity, efficiency and stability of the new lenti-Cyto-PO vector-mediated gene expression in retina-serived cells. We believe that objectives of phase I studies will be to accrue sufficient data for phase II studies that lenti-Cyto-PO vector system will be used in the retina of mice as a vehicle to transfer transgenes encoding anti-angiogenic peptides and siRNA to protect hypoxia-induced CNV. This tissue-specific lentiviral transfer system has tremendous commercial values because it will be very effective for the use of treating CNV in degenerative ocular diseases.